Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of 24 publications is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.


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  • Electrically tunable nonlinear plasmonics in graphene nanoislands (2014)

    García de Abajo, Francisco Javier (ICFO)

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    Electrically tunable nonlinear plasmonics in graphene nanoislands

    Nonlinear optical processes rely on the intrinsically weak interactions between photons enabled by their coupling with matter. Unfortunately, many applications in nonlinear optics are severely hindered by the small response of conventional materials. Metallic nanostructures partially alleviate this situation, as the large light enhancement associated with their localized plasmons amplifies their nonlinear response to record high levels. Graphene hosts long-lived, electrically tunable plasmons that also interact strongly with light. Here we show that the nonlinear polarizabilities of graphene nanoislands can be electrically tuned to surpass by several orders of magnitude those of metal nanoparticles of similar size. This extraordinary behaviour extends over the visible and near-infrared spectrum for islands consisting of hundreds of carbon atoms doped with moderate carrier densities. Our quantum- mechanical simulations of the plasmon-enhanced optical response of nanographene reveal this material as an ideal platform for the development of electrically tunable nonlinear optical nanodevices. 

  • Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signaling and PTHLH (2014)

    Gomis, Roger (IRB Barcelona)

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    Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signaling and PTHLH

    Despite improvements in diagnosis and treatment of early colorectal cancer (CRC), both first and subsequent relapse in liver and lung remain common. Patients with metastasis are treated with systemic chemotherapy, mostly in a palliative manner. Nevertheless, in selected patients with isolated liver metastasis, increased 5 year survival can be achieved by multimodal treatment that includes combination of surgery with modern chemotherapy. However, only about 25% of patients can benefit from this type of treatment and the presence of metastases in other organs is, in most cases, a contraindication for resection. Lung is the most frequently involved organ, which highlights the need to understand mechanisms of CRC lung metastasis to further improve disease control.In this manuscript, we have identified for the first time the signaling pathway mediators and effectors that drive lung metastasis from previously established liver metastasis in colon cancer. We report a set of genes whose expression supports colonization by KRASmut colorectal cancer cells and that are associated with metastasis relapse in patients with colon cancer. We have also found enhanced ERK2 activity levels both in the metastatic cell populations and in tumors from colon cancer patients with metastasis. Downregulation of ERK2 does not affect the proliferation of colon cancer cells but attenuates their ability to form liver metastasis in mice. Interestingly, ERK2 downregulation did not affect the ability of colon cancer cells to colonize the lungs, but we provide clinical and molecular evidence indicating that p38 MAPK activity is involved. In particular, we show that induction of the cytokine PTHLH, as a consequence of p38 MAPK attenuation, facilitates the seeding of the lungs by colon cancer cells growing in liver metastatic lesions facilitating the extravasation process. Altogether, our results dissect colorectal cancer metastasis mechanisms into consecutive steps of liver and lung colonization, which involve specific alterations in MAPK signaling, and highlight the implications of metastatic lesions as a platform for further dissemination.The observation that liver and lung seeding is linked to tumor-specific or circulating cell-specific factors may create opportunities for the development of targeted therapies to prevent disease dissemination from the colon to the liver, and subsequently to the lungs.

  • The first light-operated drugs for most common target proteins (2014)

    Gorostiza Langa, Pau (IBEC)

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    The first light-operated drugs for most common target proteins

    We have developed Alloswitch-1, the first light-controlled therapeutic agent whose effects focus specifically on the largest, most important class of drug target proteins – G protein-coupled receptors. Controlling drug activity with light means that the therapeutic effects can be accurately delivered locally, thus reducing their effect on other areas and the resultant side effects, and helps reduce the dosage required. Alloswitch-1 targets the metabotropic glutamate receptor mGlu5 specifically at the allosteric site of the protein. Allosteric modulators have a number of advantages over traditional drugs, offering higher selectivity of target receptors, tunable release according to whether the undesirable protein receptor activity is present, and lower potential for toxic effects. Building a photocontrolled modulator of a G protein-coupled receptor required developing a new chemical design concept in which the photoswitch is not tethered to the drug but inserted within the pharmacophore, which is the group of atoms in the molecule of a drug responsible for its action. The compound turned out to be one of the most potent and selective allosteric modulators in its class. The effects of this ‘optopharmacological’ compound can be remotely controlled in space and time in living, wildtype organisms. This is an advantage over optogenetic manipulations, which require gene overexpression using viruses, for example. Small molecule therapeutic agents as Alloswitch-1, if they can be made available orally, could offer a competitive advantage over traditional drugs, which often affect off-target tissues and organs, leading to unwanted consequences and compromising their beneficial effects.

  • Dental calculus reveals evidence for food, medicine, cooking and plant processing in prehistoric Central Sudan. (2014)

    Hardy, Karen (UAB)

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    Dental calculus reveals evidence for food, medicine, cooking and plant processing in prehistoric Central Sudan.

    Accessing information on plant consumption before the adoption of agriculture is challenging. However, there is growing evidence for use of locally available wild plants from an increasing number of pre-agrarian sites, suggesting broad ecological knowledge. The extraction of chemical compounds and microfossils from dental calculus removed from ancient teeth offers an entirely new perspective on dietary reconstruction, as it provides empirical results on material that is already in the mouth. In this paper we presented a suite of results from the multi-period Central Sudanese site of Al Khiday. We demonstrated the ingestion in both pre-agricultural and agricultural periods of Cyperus rotundus tubers. This plant is a good source of carbohydrates and has many useful medicinal and aromatic qualities, though today it is considered to be the world's most costly weed. Its ability to inhibit Streptococcus mutans may have contributed to the unexpectedly low level of caries found in the agricultural population. Other evidence extracted from the dental calculus includes smoke inhalation, dry (roasting) and wet (heating in water) cooking, a second plant possibly from the Triticaceae tribe and plant fibres suggestive of raw material preparation through chewing.Featured in National Geographic, El Mundo, Voice of America, New York Times, BBC East, BBC 5 Live, Dental Tribune International, Haaretz, Israel, Voice of America, National Public Radio Washington DC. 

  • The history of life in the universe may have been governed by the frequency of giant stellar explosions (2014)

    Jiménez Tellado, Raúl (UB)

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    The history of life in the universe may have been governed by the frequency of giant stellar explosions

    Two astronomers, Tsvi Piran of the Hebrew University of Jerusalem and Raul Jimenez, ICREA at the University of Barcelona, argue that some regions of the galaxy are less friendly to life than others. Their interest in gamma-ray bursts (GRBs), which are the most energetic phenomena yet discovered in the universe, has lead them to analyze how this powerful events could affect the chances of developing life in Earth-like planets. The idea is that a GRB occuring nearby (nearby, in this context, means within about 10,000 light-years) to an Earth-like planet, can wreck its biosphere.The pattern of GRBs shows that they have got rarer over the course of time an also that they are more likely to happen around the center of the Galaxy. Their study shows that GRBs would be common enough so that a planet, almost anywhere in the galaxy, would have suffered from at least one in the past billion years. They estimate that even now, only 10% of the universe’s galaxies would host sufficiently few GRBs to give the evolution of complex life a fair run.Their finding has attarcted mayor media attention, among others from The Economist, Science, Sci. American, CNN, etc.

  • The Decay of Consent: International Law in an Age of Global Public Goods (2014)

    Krisch, Nico (IBEI)

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    The Decay of Consent: International Law in an Age of Global Public Goods

    International law’s consent-based structure is often seen as inadequate for solving global public goods problems, and many commentators expect a turn toward non-consensualism in response. This article focuses on three issue areas to analyze whether we can indeed observe such a turn. In the resulting picture, international law retains much of its consensual character, but it is increasingly sidelined in favour of other – especially informal and unilateral – modes of governance in which consent plays a more limited role and hierarchy is often pronounced.